E-Pearl of the Week: Transthyretin amyloidosis

August 23, 2012

Familial amyloid polyneuropathies are secondary to amyloid deposits in the peripheral nervous system as a result of misfolding of mutant proteins such as transthyretin (TTR), apolipoprotein A–1, or gelsolin. The most common variety of FAP is due to dominantly inherited TTR gene mutations which are particularly prevalent in Portugal, Sweden and Japan. Patients usually present in their thirties with a distal painful sensory neuropathy followed by motor and pronounced autonomic dysfunction. Patients may benefit from liver transplantation because the mutated TTR is primarily generated in the liver. Tafamidis, a drug that may be beneficial to patients with TTR amyloidosis, occupies TTR's thyroxine binding sites, stabilizes mutated TTR tetramers and prevents misfolding of the protein.

Disclosures: Dr. Karam serves on the editorial team for the Neurology® Resident and Fellow Section.

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